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A decision support tool to find the best cyclosporine dose when switching from intravenous to oral route in pediatric stem cell transplant patients

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Managing the pharmacokinetic variability of immunosuppressive drugs after pediatric hematopoietic stem cell transplantation (HSCT) is a clinical challenge. Thus, the aim of our study was to design and validate a decision support tool predicting the best first cyclosporine oral dose to give when switching from intravenous route.

Methods

We used 10-years pediatric HSCT patients’ dataset from 2008 to 2018. A tree-augmented naïve Bayesian network model (method belonging to artificial intelligence) was built with data from the first eight-years, and validated with data from the last two.

Results

The Bayesian network model obtained showed good prediction performances, both after a 10-fold cross-validation and external validation, with respectively an AUC-ROC of 0.89 and 0.86, a percentage of misclassified patients of 28.7% and 35.2%, a true positive rate of 0.71 and 0.65, and a false positive rate of 0.12 and 0.14 respectively.

Conclusion

The final model allows the prediction of the most likely cyclosporine oral dose to reach the therapeutic target specified by the clinician. The clinical impact of using this model needs to be prospectively warranted. Respecting the decision support tool terms of use is necessary as well as remaining critical about the prediction by confronting it with the clinical context.

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Authors and Affiliations

  1. EMR 3738, Ciblage Thérapeutique en Oncologie, Faculté de Médecine et de Maïeutique Lyon-Sud Charles Mérieux, Université Claude Bernard Lyon 1, 165 chemin du Grand Revoyet-BP 12, 69921 Oullins Cedex, Lyon, France

    Vincent Leclerc, Nathalie Bleyzac & Michel Ducher

  2. Pharmacy Department, Hôpital Pierre Garraud, Groupement Hospitalier Nord, Hospices Civils de Lyon, 136 rue du Commandant Charcot, 69005, Lyon, France

    Vincent Leclerc & Michel Ducher

  3. Institute of Pediatric Hematology and Oncology (IHOPe), Hematology Unit, Hospices Civils de Lyon and Claude Bernard University, Lyon, France

    Antony Ceraulo & Yves Bertrand

Authors
  1. Vincent Leclerc
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  2. Nathalie Bleyzac
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  3. Antony Ceraulo
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  4. Yves Bertrand
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  5. Michel Ducher
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Contributions

Doctor Vincent Leclerc participated to the design of the study, the data production, the data analysis, manuscript writing, and manuscript reviewing. Doctor Michel Ducher participated to the design of the study, the data analysis, manuscript writing, and manuscript reviewing. Doctor Antony Ceraulo participated to the design of the study, the data production, and the manuscript reviewing. Professor Yves Bertrand participated to the design of the study, the data production, and the manuscript reviewing. Doctor Nathalie Bleyzac participated to the design of the study, the data production, manuscript writing, and manuscript reviewing.

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Correspondence to Vincent Leclerc.

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Leclerc, V., Bleyzac, N., Ceraulo, A. et al. A decision support tool to find the best cyclosporine dose when switching from intravenous to oral route in pediatric stem cell transplant patients. Eur J Clin Pharmacol 76, 1409–1416 (2020). https://doi.org/10.1007/s00228-020-02918-9

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